The role of DNA repair pathways in cisplatin resistant lung cancer

Platinum chemotherapeutic agents such as cisplatin are currently used in the treatment of various malignancies such as lung cancer. However, their efficacy is significantly hindered by the development of resistance during treatment. While a number of factors have been reported that contribute to the onset of this resistance phenotype, alterations in the DNA repair capacity of damaged cells is now recognised as an important factor in mediating this phenomenon. The mode of action of cisplatin has been linked to its ability to crosslink purine bases on the DNA, thereby interfering with DNA repair mechanisms and inducing DNA damage. Following DNA damage, cells respond by activating a DNA-damage response that either leads to repair of the lesion by the cell thereby promoting resistance to the drug, or cell death via activation of the apoptotic response. Therefore, DNA repair is a vital target to improving cancer therapy and reduce the resistance of tumour cells to DNA damaging agents currently used in the treatment of cancer patients. To date, despite the numerous findings that differential expression of components of the various DNA repair pathways correlate with response to cisplatin, translation of such findings in the clinical setting are still warranted. The identification of alterations in specific proteins and pathways that contribute to these unique DNA repair pathways in cisplatin resistant cancer cells may potentially lead to a renewed interest in the development of rational novel therapies for cisplatin resistant cancers, in particular, lung cancer.

Making things happen: How the environment triggers action

Innovative research conducted by Dr Jan Golembiewski from Medical Architectures Australasia-Pacific, in the area of environmental design for mental healthcare helps us reflect, through experiential storytelling, on the importance of paying attention to positive environmental ‘triggers for action’ when designing physical spaces to help manage particular patients’ conditions. This article is written about the mental health experience specifically, however environmental design is an issue we can all relate to in our everyday lives (at home, at work, social spots or in places such as hospitals or retreats) when we instinctively notice a connection between our mental health and our surroundings or a healthy sense of place.

Medical education and law: Withholding/withdrawing treatment from adults without capacity

BACKGROUND Law is increasingly involved in clinical practice, particularly at the end of life, but undergraduate and postgraduate education in this area remains unsystematic. We hypothesised that attitudes to and knowledge of the law governing withholding/withdrawing treatment from adults without capacity (the WWLST law) would vary and demonstrate deficiencies among medical specialists. AIMS We investigated perspectives, knowledge and training of medical specialists in the three largest (populations and medical workforces) Australian states, concerning the WWLST law. METHODS Following expert legal review, specialist focus groups, pre-testing and piloting in each state, seven specialties involved with end-of-life care were surveyed, with a variety of statistical analyses applied to the responses. RESULTS Respondents supported the need to know and follow the law. There were mixed views about its helpfulness in medical decision-making. Over half the respondents conceded poor knowledge of the law; this was mirrored by critical gaps in knowledge that varied by specialty. There were relatively low but increasing rates of education from the undergraduate to continuing professional development (CPD) stages. Mean knowledge score did not vary significantly according to undergraduate or immediate postgraduate training, but CPD training, particularly if recent, resulted in greater knowledge. Case-based workshops were the preferred CPD instruction method. CONCLUSIONS Teaching of current and evolving law should be strengthened across all stages of medical education. This should improve understanding of the role of law, ameliorate ambivalence towards the law, and contribute to more informed deliberation about end-of-life issues with patients and families.

Futile treatment in hospital: Doctors’ intergroup language

Treatment that will not provide significant net benefit at the end of a person’s life (called futile treatment) is considered by many people to represent a major problem in the health sector, as it can waste resources and raise significant ethical issues. Medical treatment at the end of life involves a complex negotiation that implicates intergroup communication between health professionals, patients, and families, as well as between groups of health professionals. This study, framed by intergroup language theory, analyzed data from a larger project on futile treatment, in order to examine the intergroup language associated with futile treatment. Hospital doctors (N = 96) were interviewed about their understanding of treatment given to adult patients at the end of life that they considered futile. We conducted a discourse analysis on doctors’ descriptions of futile treatment provided by themselves and their in-group and out-group colleagues. Results pointed to an intergroup context, with patients, families, and colleagues as out-groups. In their descriptions, doctors justified their own decisions using the language of logic, ethics, and respect. Patients and families, however, were characterized in terms of wishing and wanting, as were outgroup colleagues. In addition, out-group doctors were described in strongly negative intergroup language.

Inhibiting Eph kinase activity may not be “Eph”ective for cancer treatment

Several Eph receptor tyrosine kinases (RTKs) are commonly over-expressed in epithelial and mesenchymal cancers and are recognized as promising therapeutic targets. Although normal interaction between Eph receptors and their ephrin ligands stimulates kinase activity and is generally tumor suppressive, significant Eph over-expression allows activation of ligand- and/or kinase-independent signaling pathways that promote oncogenesis. Single-agent kinase inhibitors are widely used to target RTK-driven tumors but acquired and de novo resistance to such agents is a major limitation to effective clinical use. Accumulating evidence suggests that Ephs can be inhibited by “leaky” or low-specificity kinase inhibitors targeted at other RTKs. Such off-target effects may therefore inadvertently promote ligand- and/or kinase-independent oncogenic Eph signaling, thereby providing a new mechanism by which resistance to the RTK inhibitors can emerge. We propose that combining specific, non-leaky kinase inhibitors with tumor-suppressive stimulators of Eph signaling may provide more effective treatment options for overcoming treatment-induced resistance and clinical failure.

Translating Management Storylines: developing a visual strategy to communicate science to stakeholder community, a case for Mackay, QLD

This project developed a visual strategy and graphic outcomes to communicate the results of a scientific collaborative project to the Mackay community. During 2013 and 2014 a team from CSIRO engaged with the community in Mackay to collaboratively develop a set of strategies to improve the management of the Great Barrier Reef. The result of this work was a 300+ page scientific report that needed to be translated and summarised to the general community. The aim of this project was to strategically synthesise information contained in the report and to design and produce an outcome to be distributed to the participant community. By working with the CISRO researchers, an action toolkit was developed, with twelve cards and a booklet. Each card represented the story behind a certain local management issue and the actions that the participants suggested should be taken in order to improve management of The Reef. During the design synthesis it was identified that for all management issues there was a reference to the need to develop some sort of "educational campaign" to the area. That was then translated as an underlying action to support all other actions proposed in the toolkit.

Democratic and participatory citizenship: Youth action for sustainability in Australia

Purpose – The purpose of this paper is to provide a critical analysis of recent examples of action competence among young people engaged in democratic participatory action in sustainability programs in Australia. It explores examples of priorities identified for citizen action, the forms this action takes and the ways that democratic participation can achieve positive outcomes for future sustainability. It suggests multiple ways for developing action competence that provides further opportunities for authentic and engaging citizen action for youth connected to school- and community-based learning, in new and powerful ways. Design/methodology/approach – This conceptual paper examines international literature on the theory of “action competence,” its significance for education for sustainability (EfS) and the ways it can inform education for young people’s democratic participatory citizenship and civic engagement. It analyses examples of the development of action competency among young people in Australia, including the problems and priorities identified for citizen action, the forms this action takes and how it can achieve positive outcomes for sustainability. Following this analysis, the paper suggests multiple ways for developing action competence in EfS in schools and communities in new and powerful ways. Findings – Developing EfS to increase democratic and participatory action among young citizens is now widely regarded as an urgent education priority. There are growing exemplars of school and community organizations’ involvement in developing EfS learning and teaching to increase participatory citizenship. Young people are being empowered to develop a greater sense of agency through involvement in programs that develop action competence with a focus on sustainability in and out of school. New forms of participation include student action teams and peer collaboration among youth who are marshaling social media and direction action to achieve change. Originality/value – It contributes to the literature on multiple ways for developing action competence in EfS.

The National Stroke Nursing Council: A nursing call for action

Nursing is fundamental to the care of stroke patients. From the acute setting all the way to rehabilitation and community reintegration, nursing is there. Having well-educated and highly skilled nurses to monitor and care for stroke patients is crucial. Equally important is the collaboration of colleagues at a national level to facilitate and disseminate research and best practice guidelines across Canada. The National Stroke Nursing Council aims to fill this role. Stroke nurses from across Canada were invited to a national forum in 2005, hosted by the Canadian Stroke Network. The focus of this forum was to elucidate issues of concern to nurses across the stroke care continuum in relation to a Canadian Stroke Strategy. Subsequent to this forum, a cadre of nurses, after undergoing a rigorous screening process, were selected to form the inaugural National Stroke Nursing Council (NSNC). With ongoing support from the Canadian Stroke Network, the mandate of the NSNC is to promote leadership, communication, advocacy, education and nursing research in the field of stroke.

A workplace-based Participatory Action Research project to investigate the effectiveness of nutrition and physical activity interventions for truck drivers in six Queensland transport industry workplaces: 2012-2015

The Queensland Transport Industry Workplace Health Intervention project was a Participatory Action Research (PAR) project to investigate the effectiveness of workplace-based nutrition and physical activity health promotion interventions for truck drivers in transport industry workplaces in south-east Queensland. The project was conducted by a research team at the Queensland University of Technology (QUT), and was funded by the Queensland Government under the Healthier.Happier.Workplaces initiative.